Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal.

STUDY OBJECTIVES: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms. METHODS: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity. RESULTS: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (ß = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: ß = 2.579, d = 0.413, p = 0.009 | 40 mg ß = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: ß = 158.304, d = 0.397, p = 0.009 | 40 mg: ß = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: ß = 48.97, d = 0.410, p < 0.001 | 40 mg: ß = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: ß = 190.90, d = 0.308, p = 0.99 | 40 mg: ß = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: ß = 215.55, d = 0.034, p = 0.006 | 40 mg: ß = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: ß = -357.84, d = -0.659, p = 0.004 | 40 mg: ß = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: ß = 740.58, d = 0.964 p = <0.001 | 40 mg: ß = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: ß = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group. CONCLUSIONS: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal.

Letter to the Editor on "Leveraging Biomedical Engineering Engineers to Improve Obstructive Sleep Apnea (OSA) Care for Our Stroke Patients".

Obstructive sleep apnea (OSA), a condition of recurring, episodic complete or upper airway collapse, is a common disorder, affecting an estimated 17.4% of women and 33.9% of men in the United States [1]. The first line treatment for OSA is Continuous Positive Airway Pressure (CPAP) therapy, a medical device that delivers adequate airflow and oxygenation during sleep by way of a tube that connects an air compressor to a face mask that can fit over the nose, under the nose, or over the nose and mouth.

The promotion of sleep wellness: Resilience as a protective factor.

Objectives: To evaluate the association between resilience, sleep quality, and health. Methods: This cross-sectional study included 190 patients (Mean age = 51, SD = 15.57) recruited from the Johns Hopkins Center for Sleep and Wellness. Patients completed a modified version of the brief resilience scale (BRS) to assess characteristics of resilience and questions to assess aspects of mental health, physical health, sleep quality, and daytime functioning. Results: Participants' average score on the BRS was 4.67 (SD = 1.32, range = 1.17-7), reflecting a high level of resilience. There was a significant gender difference in resilience levels for men (Mean = 5.04, SD = 1.14) and women (Mean = 4.30, SD = 1.38), such that men reported significantly higher levels of resilience compared to women (t (188) = 4.02, p < 0.001) [lower levels of resilience were significantly associated with higher levels of (current) fatigue and tiredness after adjusting for demographic, physical, and mental covariates. In those reporting between one and three mental health symptoms, high levels of resilience minimized the negative influence that these symptoms had on sleep quality. This minimizing effect was no longer evident in those experiencing >3 mental health symptoms, who also reported significantly higher symptoms of fatigue despite their high resilience scores. Conclusions: This study emphasizes how resilience may affect the relationship between mental health and sleep quality in sleep patients. Resilience may further our understanding of the inter-relationships between sleep and the manifestation of physical health symptoms, a relationship that will likely heighten in relevance during personal and global crisis. An awareness of this interaction could be used as a proactive prevention and treatment strategy. In other words, incorporating methods to evaluate resilience in patients with mental illnesses regularly can be useful for predicting the potential manifestation and severity of sleep disturbance. Therefore, strategies that focus on promoting resilience could improve health and wellness.

An Integrated Interdisciplinary Sleep Care Model-The Ultimate Dream Team.

This Viewpoint discusses the need for diverse physicians to manage sleep health.

Comparative effectiveness study of flipped classroom versus online-only instruction of clinical reasoning for medical students.

CONTEXT: Bedside clinical teaching is the backbone of clerkship education. Data-driven methods for supplementing bedside encounters with standardized content from vetted resources are needed. OBJECTIVE: To compare a flipped-classroom versus an interactive online-only instruction for improving knowledge, skills, self-directed learning (SDL) behaviors, and satisfaction in a medical school clerkship. METHODS: An IRB-approved prospective study employing a peer-reviewed clinical reasoning curriculum in neurology was conducted; 2nd-4th year medical students rotating through a required clerkship were enrolled. Students were randomized to flipped-classroom (i.e., flipped) or interactive asynchronous online instruction (i.e., online-only), which supplemented existing bedside teaching. Baseline and end-of-course knowledge, skill development, SDL behaviors, satisfaction, and long-term retention were assessed by peer-reviewed clinical reasoning exam, NBME scores, faculty/resident clinical evaluations, non-compulsory assignment completion, end-of-clerkship surveys, and objective structured clinical exam (OSCE). RESULTS: 104 students (49 flipped, 55 online-only) were enrolled. Age, gender, and training level did not differ by group (all p > 0.43); baseline knowledge was higher in the flipped group (p = 0.003). Knowledge-based exam scores did not differ by group even after adjusting for differences in baseline knowledge (2.3-points higher in flipped group, 95%CI -0.4-4.8, p = 0.07). Clinical skills were significantly higher in the flipped group, including examination skills (4.2 ± 0.5 vs. 3.9 ± 0.7, p = 0.03) and future housestaff potential (4.8 ± 0.3 vs 4.5 ± 0.6, p = 0.03). Students in the online-only group were more likely to engage in SDL (42 vs. 12%, p = 0.001) and reported more hours studying (6.1 vs. 3.8 hours, p = 0.03). Satisfaction (p = 0.51) and OSCE scores (p = 0.28) were not different by group. CONCLUSIONS: In this comparative study of two evidence-based curricular delivery approaches, we observed no difference in knowledge acquired. Greater clinical skills were observed with flipped instruction, while more SDL was observed with online-only instruction. Supplementing bedside teaching with blended instruction that balances live skill development with vetted online resources is optimal for clerkship education.

It's a Win-Win: The Effect of Medical Students on Clinic Productivity.

Objective: We sought to explore whether obstetrics and gynecology (Ob-Gyn) ambulatory clinic preceptors can maintain their clinical productivity with a learner (medical student) present. Methods: We studied the productivity of five exemplary Ob-Gyn faculty over the 2016-2017 academic year. We used paired two-tailed t tests to compare physician productivity with and without a student. Faculty were interviewed and qualitative analyses were performed on faculty interview data to identify themes used to create sample best-practice workflows for student involvement in the clinic. Results: Three faculty had significant increases in relative value units (RVUs) per clinic half-day when a medical student was present (11%-31% increase, P<.05). Four faculty had average increases in net charges billed per clinic half-day ranging from $172.39 to $343.14. One faculty preceptor had a decrease in RVUs and charges billed when a student was present, which was not statistically significant. Themes derived from faculty interviews regarding their incorporation of medical students in the clinic included setting expectations, allowing students to assist with clinic workflow, note-writing, and efficient use of time and clinic space. In an iterative feedback process, we developed ideal workflow models for student involvement during clinic visits with and without a procedure. Conclusion: This mixed-methods pilot study suggests that medical students do not impede clinician productivity when utilized effectively in the outpatient setting. Further contemporary research is needed to assess the impact of learners on ambulatory clinician productivity in light of Medicare policy changes and modifications in medical education due to the COVID-19 pandemic.

Suvorexant ameliorated sleep disturbance, opioid withdrawal, and craving during a buprenorphine taper.

Increased orexin/hypocretin signaling is implicated in opioid withdrawal, sleep disturbances, and drug-seeking behaviors. This study examined whether a dual-orexin receptor antagonist would improve sleep and withdrawal outcomes when compared with placebo during a buprenorphine/naloxone taper. Thirty-eight participants with opioid use disorder were recruited to a clinical research unit and maintained on 8/2 to 16/4 mg of buprenorphine/naloxone treatment for 3 days before being randomized to 20 mg of suvorexant (n = 14), 40 mg of suvorexant (n = 12), or placebo (n = 12); 26 individuals completed the study. After randomization, participants underwent a 4-day buprenorphine/naloxone taper and 4-day post-taper observation period. Total sleep time (TST) was collected nightly with a wireless electroencephalography device and wrist-worn actigraphy; opioid withdrawal symptoms were assessed via the Subjective Opiate Withdrawal Scale (SOWS); and abuse potential was assessed on a 0- to 100-point visual analog scale of "High" every morning. A priori outcomes included two-group (collapsing suvorexant doses versus placebo) and three-group comparisons of area-under-the-curve (AUC) scores for TST, SOWS, and High. In two-group comparisons, participants receiving suvorexant displayed increased TST during the buprenorphine/naloxone taper and decreased SOWS during the post-taper period. In three-group comparisons, participants receiving 20 mg of suvorexant versus placebo displayed increased AUC for TST during the buprenorphine/naloxone taper, but there was no difference in SOWS among groups. There was no evidence of abuse potential in two- or three-group analyses. The results suggest that suvorexant might be a promising treatment for sleep and opioid withdrawal in individuals undergoing a buprenorphine/naloxone taper.

Wireless electroencephalography (EEG) to monitor sleep among patients being withdrawn from opioids: Evidence of feasibility and utility.

Sleep impairment is a common comorbid and debilitating symptom for persons with opioid use disorder (OUD). Research into underlying mechanisms and efficacious treatment interventions for OUD-related sleep problems requires both precise and physiologic measurements of sleep-related outcomes and impairment. This pilot examined the feasibility of a wireless sleep electroencephalography (EEG) monitor (Sleep Profiler™) to measure sleep outcomes and architecture among participants undergoing supervised opioid withdrawal. Sleep outcomes were compared to a self-reported sleep diary and opioid withdrawal ratings. Participants (n = 8, 100% male) wore the wireless EEG 85.6% of scheduled nights. Wireless EEG detected measures of sleep architecture including changes in total, NREM and REM sleep time during study phases, whereas the diary detected changes in wakefulness only. Direct comparisons of five overlapping outcomes revealed lower sleep efficiency and sleep onset latency and higher awakenings and time spent awake from the wireless EEG versus sleep diary. Associations were evident between wireless EEG and increased withdrawal severity, lower sleep efficiency, less time in REM and non-REM stages 1 and 2, and more hydroxyzine treatment; sleep diary was associated with total sleep time and withdrawal only. Data provide initial evidence that a wireless EEG is a feasible and useful tool for objective monitoring of sleep in persons experiencing acute opioid withdrawal. Data are limited by the small and exclusively male sample, but provide a foundation for using wireless EEG sleep monitors for objective evaluation of sleep-related impairment in persons with OUD in support of mechanistic and treatment intervention research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Worsening sleep quality across the lifespan and persistent sleep disturbances in persons with opioid use disorder.

STUDY OBJECTIVES: Individuals with opioid use disorder (OUD) may experience worsening sleep quality over time, and a subset of individuals may have sleep disturbances that precede opioid use and do not resolve following abstinence. The purpose of the present study was to (1) collect retrospective reports of sleep across the lifespan and (2) identify characteristics associated with persistent sleep disturbance and changes in sleep quality in persons with OUD. METHODS: Adults with OUD (n = 154) completed a cross-sectional study assessing current and past sleep disturbance, opioid use history, and chronic pain. Repeated-measures analysis of variance was used to examine changes in retrospectively reported sleep quality, and whether changes varied by screening positive for insomnia and/or chronic pain. Multivariate linear regression analyses were used to identify additional correlates of persistent sleep disturbance. RESULTS: Participants reported that their sleep quality declined over their lifespan. Changes in reported sleep over time varied based on whether the individual screened positive for co-occurring insomnia and/or chronic pain. In regression analyses, female sex (ß = 0.16, P = .042), a greater number of treatment episodes (ß = 0.20, P = .024), and positive screens for chronic pain (ß = 0.19, P = .018) and insomnia (ß=0.22, P = .013) were associated with self-reported persistent sleep disturbance. Only a portion of participants who screened positive for sleep disorders had received a formal diagnosis. CONCLUSIONS: OUD treatment providers should routinely screen for co-occurring sleep disturbance and chronic pain. Interventions that treat co-occurring OUD, sleep disturbance, and chronic pain are needed. CITATION: Ellis JD, Mayo JL, Gamaldo CE, Finan PH, Huhn AS. Worsening sleep quality across the lifespan and persistent sleep disturbances in persons with opioid use disorder. J Clin Sleep Med. 2022;18(2):587-595.

Clinical correlates of drug-related dreams in opioid use disorder.

BACKGROUND AND OBJECTIVES: Drug-related dreams are commonly reported by individuals in treatment for substance use disorders, which may be distressing. Existing evidence suggests that dream recollection may be influenced by clinically relevant phenomena, such as opioid use and withdrawal, general sleep disturbance, affective symptoms, and chronic pain. However, very few studies have explored drug-related dreams among individuals who screened positive for opioid use disorder (OUD). METHODS: Adults recruited from Amazon Mechanical Turk (MTurk) who screened positive for OUD (N = 154) completed a questionnaire about drug-related dreams, as well as measures assessing sleep, opioid use history, stress, anxiety, and chronic pain. χ2 analyses, one-way analysis of variance, and bivariate correlations, correcting for the false discovery rate, were used as appropriate to explore correlates of (1) recollecting a drug-related dream, and (2) experiencing post-dream craving and distress. RESULTS: Individuals who recollected a past-week drug-related dream were more likely to report other recent sleep disturbances, including poorer sleep quality, greater insomnia symptoms, and a higher risk for sleep apnea. Post-dream craving and distress were both associated with greater insomnia symptoms, poor sleep hygiene behaviors, and greater anxiety symptoms. Individuals who had ever experienced a drug-related dream (recently, or in their lifetime) were more likely to report a history of severe withdrawal, overdose, and intravenous opioid use. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Drug-related dreams were common among individuals in the present sample and were related to other clinically relevant phenomena. Interventions that treat co-occurring OUD, pain, sleep symptoms, and affective symptoms may improve overall well-being in this population.

Broadening learning communities during COVID-19: developing a curricular framework for telemedicine education in neurology.

BACKGROUND: In response to the cancellation of clinical clerkships due to COVID-19, the Johns Hopkins (JH) Neurology Education Team developed a virtual elective to enhance medical students' clinical telemedicine skills and foster community between academic institutions. METHODS: This two-week clinical elective, entitled "Virtual Patient Rounds in Neurology," was administered once in April 2020 and once in May 2020. The curriculum included attending/fellow-led Virtual Rounds, Student Presentations, and Asynchronous Educational Activities. We also developed a new lecture series entitled JHNeuroChats, which consisted of live synchronous lectures presented by JH faculty and Virtual Visiting Professors. Trainees and faculty from outside institutions were invited to participate in the JHNeuroChats. Students and faculty completed pre- and post-elective surveys to assess the educational impact of the elective. Student's t-tests were used to compare scores between pre- and post-elective surveys. RESULTS: Seven JH medical students enrolled in each iteration of the elective, and an additional 337 trainees and faculty, representing 14 different countries, registered for the JHNeuroChats. We hosted 48 unique JHNeuroChats, 32 (66.7%) of which were led by invited Virtual Visiting Professors. At the end of the elective, students reported increased confidence in virtually obtaining a history (P < 0.0001) and performing a telehealth neurological physical exam (P < 0.0001), compared to the start of the course. In addition, faculty members reported increased confidence in teaching clinical medicine virtually, although these findings were not statistically significant (P = 0.15). CONCLUSIONS: Despite the constraints imposed by COVID-19, this virtual Neurology elective increased medical students' confidence in certain telemedicine skills and successfully broadened our learning community to encompass learners from around the world. As virtual medical education becomes more prevalent, it is important that we are intentional in creating opportunities for shared learning across institutions. We believe that this elective can serve as a model for these future educational collaborations.

Contemporary Neuroscience Core Curriculum for Medical Schools.

Medical students need to understand core neuroscience principles as a foundation for their required clinical experiences in neurology. In fact, they need a solid neuroscience foundation for their clinical experiences in all other medical disciplines also, because the nervous system plays such a critical role in the function of every organ system. Due to the rapid pace of neuroscience discoveries, it is unrealistic to expect students to master the entire field. It is also unnecessary, as students can expect to have ready access to electronic reference sources no matter where they practice. In the pre-clerkship phase of medical school, the focus should be on providing students with the foundational knowledge to use those resources effectively and interpret them correctly. This article describes an organizational framework for teaching the essential neuroscience background needed by all physicians. This is particularly germane at a time when many medical schools are re-assessing traditional practices and instituting curricular changes such as competency-based approaches, earlier clinical immersion, and increased emphasis on active learning. This article reviews factors that should be considered when developing the pre-clerkship neuroscience curriculum, including goals and objectives for the curriculum, the general topics to include, teaching and assessment methodology, who should direct the course, and the areas of expertise of faculty who might be enlisted as teachers or content experts. These guidelines were developed by a work group of experienced educators appointed by the Undergraduate Education Subcommittee (UES) of the American Academy of Neurology (AAN). They were then successively reviewed, edited, and approved by the entire UES, the AAN Education Committee, and the AAN Board of Directors.

Training in Neurology: Implementation and Evaluation of an Objective Structured Clinical-Examination Tool for Neurology Postgraduate Trainees in Lusaka, Zambia.

BACKGROUND: We established Zambia's first neurology residency program at the University of Zambia School of Medicine and the University Teaching Hospital in Lusaka. OBJECTIVE: To evaluate the feasibility and effectiveness of a modified objective structured clinical examination (OSCE) to assess clinical skills. METHODS: The neurology training program's 3 participants completed the OSCE exercise in February 2019. We used smartphones to videotape trainees performing a physical examination and oral presentation in the neurology clinic. Trainees and faculty reviewed the videos independently using a standardized rubric and then met for in-person feedback. RESULTS: Three trainees completed pre- and post-OSCE surveys rating their confidence in elements of the history and examination. Trainees' average self-confidence scores improved from the pre- to post-OSCE survey in every category (pre-OSCE: mean score 6.84, range 4.8-7.8, SD 0.92; post-OSCE: mean score 7.9, range 5.67-9.33, SD 0.86). Qualitative feedback showed trainees found the OSCE helpful, routinely applied feedback, and would appreciate repeating OSCEs. CONCLUSIONS: OSCEs improve trainees' self-confidence and can be modified and successfully implemented in a resource-limited neurology postgraduate training program. Important OSCE modifications involved using smartphones for videotaping and a real patient encounter rather than a standardized patient. Embedding the experience within a busy clinic day was practical, applicable, and efficient. Future work should expand use of OSCEs both within the Zambian neurology residency program and non-neurology training programs. Including additional video reviewers could add to the validity of clinical skills assessment. Videos could also be used for remote mentorship and teaching purposes.

Assessing Sleep Concerns in Individuals With Acquired Brain Injury: The Feasibility of a Smartpad Sleep Tool.

OBJECTIVE: The investigators examined the presence of disrupted sleep in acquired brain injury (ABI) and the utility of a mobile health program, MySleepScript, as an effective clinical tool to detect sleep disturbances. METHODS: A cross-sectional pilot study of MySleepScript, a customizable electronic battery of validated sleep questionnaires, was conducted. Participants were recruited at the Acquired Brain Injury Clinic at Johns Hopkins Bayview Medical Center. RESULTS: Sixty-eight adults with ABI (mean age, 46.3 years [SD=14.8]) participated in the study, with a mean completion time of 16.6 minutes (SD=5.4). Time to completion did not differ on individual completion or staff assistance. The mean score on the Pittsburgh Sleep Quality Index was 9.2 (SD=4.7); 83.9% of individuals had poor sleep quality (defined as a score >5). Insomnia Severity Index scores indicated moderate to severe insomnia in 45% of participants; 36.5% of participants screened positive for symptoms concerning sleep apnea, while 39.3% of individuals screened positive for restless legs syndrome. CONCLUSIONS: Poor sleep quality was highly prevalent in this ABI cohort. MySleepScript may be an effective method of assessing for sleep disturbance in ABI. Further efforts to identify sleep disorders in this patient population should be pursued to optimize ABI management.

Identifying Sleep Biomarkers to Evaluate Cognition in HIV.

Sleep disturbance and cognitive impairment represent two of the most common and debilitating conditions facing seropositive (HIV+) individuals who are otherwise well controlled with antiretroviral therapy. Sleep-assessment-based biomarkers represent an important step towards improving our understanding of the unique mechanistic features that may link sleep disruption and cognition in HIV+ individuals, ultimately leading to advancements in treatment and management options. In this study, a risk score was computed via a generalized linear model (GLM), which optimally combines polysomnography (PSG) features extracted from EEG, EMG, and EOG signals, to distinguish 18 HIV+ Black male individuals with and without cognitive impairment. The optimal set of features was identified via the least absolute shrinkage and selection operator (LASSO) approach, and the risk separation between the two groups, i.e., cognitively normal and cognitive impaired, was significant (and has a P-value < .001). The optimal set of predictive features were all EEG derived and sleep stage-specific. These preliminary findings suggest that sleep-based EEG features may be used as both diagnostic and prognostic biomarkers for cognition in HIV+ subjects.

Optimizing Behavioral Sleep Strategies.

Patients are increasingly looking to optimize sleep as a health and wellness strategy. Sleep health is often individualized based on three elements that correspond to overall physical and mental well-being: (1) sleep quality, which refers to the continuity and depth of sleep as well as a feeling of restoration upon awakening; (2) sleep quantity, which refers to the duration of sleep that is appropriate for a given age group; and (3) timing of the sleep window, which refers to the positioning of sleep that is aligned with an individual's circadian rhythm for sleep or an ideal circadian zone. In the past, prescribing hypnotic medications was considered the primary approach for improving sleep. However, there has been a recent paradigm shift to favor behavioral approaches, particularly in the case of insomnia where cognitive-behavioral therapy has been shown to have a more favorable benefit-to-harm profile than medications. The clinical vignette is presented here as a springboard for discussion regarding the latest evidence and efficacy for sleep behavior techniques and consumer monitoring devices developed to improve sleep health and awareness for clinicians to consider when educating their patients on maximizing sleep health behaviors.